Trials avoid high risk patients and underestimate drug harms

It's understandable that unusual patients are seen as confounding variables in any study, especially those with small numbers of patients. Though I haven't read beyond the abstract, it also makes sense that larger studies (phase 3 or 4) should not exclude such patients, but perhaps could report results in more than one way -- including only those with the primary malady as well as those with common confounding conditions.

Introducing too many secondary conditions in any trial is an invitation for the drug to fail safety and/or efficacy due to increased demands on both. And as we all know, a huge fraction of drugs fail in phase 3 already. Raising the bar further, without great care, will serve neither patients nor business.

It seems like the current situation is doing a disservice to "unusual" patients (who may actually make up the majority of patients).

how do you figure? absolute SAE rate increases 2 percentage points. nothing changes about relative SAE rate. does it change anything about your choice between different health technologies? no.